AB0152 MITOCHONDRIAL DNA IS ELEVATED IN PLASMA OF PATIENTS WITH GIANT CELL ARTERITIS
Authors: S. Giaglis, D. Kyburz, N. Venhoff, U. Walker
Journal: Annals of the Rheumatic Diseases (2022)

Background Giant cell arteritis (GCA) represents the most prevalent form of systemic vasculitis in elderly, and characterized by a remarkable heterogeneity regarding clinical and histological phenotype, pathogenetic mechanisms and treatment choice (1). The pathophysiology of GCA is driven by an interplay between cells of both innate and adaptive immune systems (2). Neutrophils seem to hold a cardinal role in GCA pathology, given their abundance in vicinity to the foci of tissue injury (3). Most importantly, neutrophils eject neutrophil extracellular traps (NETs) which are decorated with a series of immunocompetent epitopes, essential for the dissemination of the inflammatory response (3, 4). Objectives The diagnostic and prognostic value of cell-free DNA in GCA is still unknown. The aim of the present study was therefore to examine the clinical utility of cell-free DNA quantification as a biomarker in GCA. Methods Total DNA was isolated from platelet-free plasma samples of matched healthy controls (HC) and consecutive GCA patients. Plasma and clinical data were collected at baseline and follow-up. Copy numbers were quantified by quantitative PCR for mtDNA (ATP-6 gene) and nuclear (n) DNA (GAPDH gene) (5). Results Twenty-one GCA patients (median age 64.0 ± 9.0, 49% female) and 22 sex matched HC were enrolled for analysis. mtDNA levels were significantly elevated in GCA plasma (2.0x10 8 copies/ml plasma, 95% CI: 7.0x10 7 to 3.8x10 8 ), compared to HC plasma (7.0x10 6 copies/ml plasma, 95% CI: 2.8x10 6 to 1.1x10 7 , p&lt;0.0001). nDNA levels in contrast did not differ between GCA (5.1x10 6 copies/ml plasma, 95%CI: 2.5x10 6 to 9.5x10 7 ) and HC (4.1x10 6 copies/ml plasma, 95%CI: 2.3x10 6 to 9.3x10 7 , p=0.74). Receiver operating characteristic curve analysis showed that a cut-off value of 2.8x10 7 mtDNA copy numbers differentiated between GCA and HC with 90.5% sensitivity, 95.2% specificity and an AUC of 0.95. There was no association of mtDNA elevation with any particular type of intra-, extra-cranial or ocular vessel involvement). Conclusion The quantification of cell free mtDNA - but not nDNA - copy numbers allows a sensitive and specific distinction between healthy individuals and patients with GCA and raises the possibility that circulating nucleic acids contribute to the pathogenesis of GCA. Plasma mtDNA quantification may aid in the diagnosis of GCA and in monitoring GCA activity. References [1]Dejaco, C., et al. Nat Rev Rheumatol 13, 578–592 (2017). [2]Salvarani, C., et al. Nat Rev Rheumatol 8, 509–521 (2012). [3]Wang L., et al. JCI Insight 5, (2020). [4]Palamidas D. A., et al. Rheumatology (Oxford), keab505 (2021). [5]Giaglis S, et al. RMD Open 2021; 7 :e002010.(2021) Figure 1. (a.) Plasma mtDNA levels in GCA patients are elevated (2 orders of magnitude) compared to healthy controls. Whiskers represent 95% CI. (b.) Receiver operating characteristic curve for mtDNA plasma concentrations discriminate between HC and GCA patients. AUC: area under the curve. Disclosure of Interests None declared